Amine thiophiles

Enhancing the utility of the allq lation-rearrangenient sequence in synthesis, the Evans group addressed the problems of a-versus-y alkylation as well as low anion reactivity by employing heterocyclic sulfides as the alleviation substrates tScheme IR.IfiE For instance, allylic imidazolyl sulfide 56 could be allqvlated efficiently, reaction at the a-position being favored by a chelated but reactive allyl lithium intermediate. Oxidation of 57 to the allylic sulfoxide and treatment with a secondary amine thiophile provided allylic alcohol 58 in high yield and with excellent stereoselectivity at the trisubstituted alkene. Allylic oxidation with manganese dioxide completed a synthesis of the sesquiterpene nuciferal (59). ... 

Owing to the reversible nature of the allylic sulfenate/allylic sulfoxide interconversion, the stereochemical outcome of both processes is treated below in an integrated manner. However, before beginning the discussion of this subject it is important to point out that although the allylic sulfoxide-sulfenate rearrangement is reversible, and although the sulfenate ester is usually in low equilibrium concentration with the isomeric sulfoxide, desulfurization of the sulfenate by thiophilic interception using various nucleophiles, such as thiophenoxide or secondary amines, removes it from equilibrium, and provides a useful route to allylic alcohols (equation 11). 

A comparatively large selection of thioureas can be formed from the reaction of amines with isothiocyanates, hence they are attractive starting materials for formation of guanidines. A common solution-phase approach to this reaction involves abstraction of the sulfur via a thiophillic metal salt, like mercuric chloride.10 For solid-phase syntheses, however, formation of insoluble heavy-metal sulfides can have undesirable effects on resin properties and on biological assays that may be performed on the product. A more relevant strategy, with respect to this chapter, is S-alkylation of thioureas and then reaction of the methyl carbamimidothioates formed (e.g., 5, Scheme 6) with amines. This type of process has been used extensively in solution-phase syntheses.1 Ul4 Two examples are shown in Scheme 6 11 the second is an intramolecular variant, which involves concomitant detrity-lation.15... 

The situation with OH and R3N is similar. Both nucleophiles are too weak thiophiles to open an S-S bond. However, sulfur chemists know that alkalies and amines tend to decompose polysulfiir compounds very effectively. This is due to secondary reactions of these nucleophiles with the ubiquitous traces of either H2S or SO2, resulting in the formation of the strong thiophiles HS or SOs (equations 141-144). 456... 

These allylic sulfoxides 41 are in equilibrium with a sulfenate ester 43 by a [2,3]-sigmatropic rearrangement 41a. It is not usually possible to detect the sulfenate ester by NMR so there must be less than about 3% of it, but it can be trapped by various nucleophiles that like to attack sulfur. These thiophiles include secondary amines, thiolate anions and, most important, phosphite esters. The reaction is carried out in a protic solvent (usually the alcohol already present in the phosphite ester) and a rearranged allylic alcohol 45 is formed. 

Thiophilic addition with protonation sulfonylation of alcohols, amines... 

Bohme and Pindur166 have reported an interesting set of reactions of alkanesulfonyl chlorides with bis-dimethylaminomethane. They appear to involve the sulfene, perhaps with thiophilic addition to form the sulfene-aminal adduct , plus a small amount of carbophilic addition, to account for the products (74, 75, 76 and 77) from 2-propa-nesulfonyl chloride alternative routes to two of the intermediates are shown with dotted arrows in equation 53. 

Fluorothiiranes are readily desulfurized by a variety of reagents. Triphenylpho-sphine, for example, reacted at RT with aminosulhde 102 to yield Dewar pyrrole 103. °° For the desulfurization of azo compound 104, a nonbasic thiophile was required because of the extremely facile azo-to-hydrazone isomerization. An imi-dazolethione accomplished this catalytically and cleanly to give 105 plus elemental sulfur, presumably via zwitterion 106. ° Thiirane 30 was transformed into perfluor-oisobutylene (107) by both amines and antimony pentafluoride. ... 

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